Variant 16-77193774-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014940.4(MON1B):c.472G>A(p.Ala158Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,454,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MON1B
NM_014940.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

MON1B (HGNC:25020): (MON1 homolog B, secretory trafficking associated) Involved in early viral transcription and late viral transcription. Located in cytoplasm. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2022]

MON1B links:

MON1B (HGNC:):

MON1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MON1B	NM_014940.4 linkuse as main transcript	c.472G>A	p.Ala158Thr	missense_variant	3/6	ENST00000248248.8	NP_055755.1	Q7L1V2-1Q6ZR87
MON1B	NM_001286639.2 linkuse as main transcript	c.149-561G>A		intron_variant			NP_001273568.1	Q7L1V2E7EW32Q6ZR87B4DKA0
MON1B	NM_001286640.2 linkuse as main transcript	c.38-561G>A		intron_variant			NP_001273569.1	Q7L1V2-2Q6ZR87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MON1B	ENST00000248248.8 linkuse as main transcript	c.472G>A	p.Ala158Thr	missense_variant	3/6	1	NM_014940.4	ENSP00000248248.3		Q7L1V2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245346

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1454044

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

722108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000633

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.472G>A (p.A158T) alteration is located in exon 3 (coding exon 2) of the MON1B gene. This alteration results from a G to A substitution at nucleotide position 472, causing the alanine (A) at amino acid position 158 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.018

D;T;D

Polyphen

0.47

.;P;.

Vest4

0.25

MutPred

0.83

Gain of phosphorylation at A158 (P = 0.0789);Gain of phosphorylation at A158 (P = 0.0789);Gain of phosphorylation at A158 (P = 0.0789);

MVP

0.30

MPC

0.57

ClinPred

0.69

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.19

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over